ProjectSummary: Over the last two decades, enabled by progress in synchrotron radiation techniques, molecular biology methods,andcomputationalresources,therehasbeentremendousprogressindeterminingthestructure ofbiomoleculesthathasled,inmanycases,todeepstructuralinsights.Butthereisathirddimensionto biological function, namely dynamics, which is, as yet, underexplored. This has created a serious blind spot that inhibits progress towards a full understanding of macromolecular functions and biological processes. The broad objective of this proposal is to develop and utilize computer simulations that addressthisdeficiencyinknowledgebyrigorouslymodelingbiomoleculardynamicsinordertoincrease ourunderstandingofbiologicalprocesses.Morespecifically,wewillpursuethreeinterrelatedprojects. First, we will determine how chromatin remodeling factors influence the dynamics of nucleosomes and chromatinfibersasameansofregulatinggeneexpression.Second,wewillexaminethemechanismsof recognitionandregulationbysortaseenzymes,whicharekeyvirulencefactorsinGram-?positivebacteria. Finally,wewilldevelopcomputationalmethodsthatmoreeffectivelymodeltheresultsofsolutionsmall angle X-?ray scattering (SAXS) experiments for diverse biomolecular complexes. Completion of these studieswillrevealintricatedetailsabouttherelationshipbetweenthestructure,function,anddynamics ofmulticomponentbiomolecularcomplexesacrossavastrangeoftimeandlengthscales.Furthermore, thesynergybetweenthescientificgoals,aswellasthecomputationalmethodsandstrongexperimental collaborationsineachoftheseprojects,willfosternewopportunitiesandareasofscientificinquirythat theMIRAawardwillallowustopursue.Overall,thisworkwilladdressaseriesoffundamentalgapsin knowledge for critical biological processes, and will lay the foundation for future studies that will improvethetreatmentandpreventionofhumanailments.